Vascular Contributions to Dementia and Genetic Risk Factors (PPG) [Includes PPG, PPG-AA, PPG-II]

This program aims to address the critical need for research into age-related diseases causing dementia, particularly Alzheimer’s disease (AD), the leading cause of cognitive decline in older adults, affecting over 5 million Americans. It focuses on investigating vascular contributions to dementia and AD by testing the neurovascular hypothesis, which proposes that cerebrovascular dysfunction is a key factor in cognitive decline. Using advanced molecular and imaging techniques, the researchers will conduct parallel studies in humans and animal models, advancing understanding and identifying potential therapeutic targets for dementia and AD treatment.

Read more about joining the PPG study here: English | Spanish

Direct: (213) 821-7158

Clinic: (323) 442-7600

Vascular Cohort Study (VCD) [Includes VCD Pilot, VCD, VCS-II]

For many years, the central scientific theme of the USC ADRC has focused on vascular contributions to cognitive impairment and Alzheimer disease (AD). Epidemiologic studies have demonstrated that traditional cardiovascular risk factors, such as hypertension and diabetes mellitus, are linked to increased risk of AD, especially among under-represented ethnic groups. The Vascular Cohort Study (VCD) is a longitudinal study directly funded by the ADRC that interrogates the health of the neurovascular unit (NVU) using novel imaging and CSF biomarkers. Using dynamic contrast enhancement (DCE)-MRI, our Imaging Core has developed a novel Ktrans measure of permeability of the blood brain barrier (BBB), one of the essential functions of the NVU. Using the Meso Scale Discovery Platform, the Biomarker Core has developed a new panel of vascular, BBB, and NVU biomarkers including cell-specific markers of pericyte, neuronal, and astroglial injury, inflammatory biomarkers, as well as AD standard Aβ and tau biomarkers that can be obtained using small quantities (0.5 ml) of CSF. Criteria for participant enrollment include age > 60 years, no or mild cognitive impairment, and presence of low, medium or high cardiovascular risk based on blood pressure, lipids, and glucose. Participants are followed annually by the Clinical Core using the NACC Uniform Data Set.

Biomarkers of ABCA1 mediated functions in Alzheimer’s (VCSGT)

The VCS-GT study is a longitudinal cohort aimed at investigating the impact of diabetes on brain connectivity. By tracking participants over time, the study seeks to understand how diabetes influences the brain’s neural networks and contributes to cognitive changes. This research could provide valuable insights into the relationship between diabetes and brain health, potentially guiding future prevention and treatment strategies.

Diverse VCID (DVCID)

As awareness of dementia increases, it is becoming common to see individuals presenting for clinical assessment with minor cognitive complaints. Neuroimaging studies frequently identify "incidental" WMH, usually ascribed to "microvascular disease" by radiologists, raising patient concerns about their brain health and future risk for dementia. To date, however, we are not aware of any studies that have comprehensively examined the impact of individual and combined MRI measures of white matter injury on cognitive performance among a diverse, non-demented, stroke free population with cognitive complaints over an extended period of observation. To address this important gap in scientific knowledge, the Diverse Vascular Cognitive Impairment project was funded by the NINDS to recruit 2250 Americans from non-Hispanic White, Black/African or Hispanic/Latino heritage to participate in a 6-year study that includes cognitive and diagnostic assessment, blood sampling for DNA and fluid biomarkers as well as 3 MRI measures. The goals of this study are to:
1) Identify the extent and characteristics of white matter injury that influence cognitive and health outcomes;
2) Evaluate Mechanisms of progression of White Matter (WM) Injury on Cognition and Health Outcomes; and
3) Based on these findings, build and validate a predictive risk model with the ultimate goal of increasing the understanding of precision medical management and planning needed by patients with white matter lesions, both for need for care as well as inclusion criteria for future therapeutic studies.

Model-based cerebrovascular markers (DVR)

The DVR project studies how changes in the dynamic regulation of brain blood flow and cortical oxygenation (called together cerebral perfusion) relate to cognitive function and memory impairment. Researchers found that people with Mild Cognitive Impairment (MCI) and mild Alzheimer’s disease (AD) show different dynamic responses to changes in blood carbon dioxide (CO2) compared to healthy people. This response is known as Dynamic Vasomotor Reactivity (DVR). Using advanced analysis of continuous tracking of cerebral blood flow and cortical oxygenation over time, the team developed a new measure called the Cerebrovascular Dynamics Index (CDI). The CDI has been shown to diagnose MCI and mild AD more accurately than brain scans or memory tests like MMSE and MoCA. It can also better distinguish between MCI and mild AD. These results suggest that the dysregulation of brain blood flow dynamics may play an important role in initiating the process of Alzheimer’s disease, along with the accumulation of amyloid-beta and p-tau proteins. While more research is needed to confirm these findings with larger cohorts, CDI offers a promising new way to diagnose and track the course of MCI and AD reliably, quickly, comfortably, and affordably.

DHA Delivery to Brain Pilot Study (DHA2BRP)

The DHA2BRP study aims to investigate the relationship between DHA intake and cognitive function, particularly in individuals with the APOE e4 gene variant. While observational studies suggest a link between DHA and cognitive health, randomized control trials show conflicting results. Preliminary data suggest that APOE e4 carriers may have lower DHA levels in cerebrospinal fluid (CSF) compared to non-carriers. The study hypothesizes that APOE e4 carriers have impaired delivery of DHA to the CSF following supplementation. To test this, researchers will measure DHA in red blood cell membranes and CSF, including apoE particles, in a pilot group of 16 APOE e4 carriers and 16 non-carriers at baseline and after 24 weeks of supplementation.

Standardized Centralized Alzheimer’s & Related Dementias Neuroimaging (SCAN)

The overarching theme of the USC ADRC is to elucidate vascular contributions to Alzheimer disease (AD), among diverse populations. Treatable cardiovascular risk factors are particularly prevalent among the Latinx population, but it remains unclear whether the epidemiological associations between cardiovascular risk factors and AD result from increased amyloidosis and tauopathy or reflect the additive effect of cerebrovascular disease. The addition of amyloid and tau PET scans, combined with advanced, high field MRI protocols which interrogate blood-brain barrier (BBB) integrity, vascular morphometry, arterial pulsatility, perivascular spaces, and cerebral blood flow will enable elucidation of these distinct pathophysiological pathways. The two-fold goals of this supplement are to contribute standardized amyloid-PET, tau-PET, and MRI neuroimaging studies on a sample of 30 elderly Latinx (> 60 years of age) to SCAN and to promote ADRD research in Latinx across all USC ADRC cores and affiliated studies. The USC ADRC participates in the national SCAN consortium funded by an administrative supplement from the National Institute on Aging.